Advanced Science (Jul 2024)

Heparan Sulfate Chain‐Conjugated Laminin‐E8 Fragments Advance Paraxial Mesodermal Differentiation Followed by High Myogenic Induction from hiPSCs

  • Mingming Zhao,
  • Yukimasa Taniguchi,
  • Chisei Shimono,
  • Tatsuya Jonouchi,
  • Yushen Cheng,
  • Yasuhiro Shimizu,
  • Minas Nalbandian,
  • Takuya Yamamoto,
  • Masato Nakagawa,
  • Kiyotoshi Sekiguchi,
  • Hidetoshi Sakurai

DOI
https://doi.org/10.1002/advs.202308306
Journal volume & issue
Vol. 11, no. 26
pp. n/a – n/a

Abstract

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Abstract Human‐induced pluripotent stem cells (hiPSCs) have great therapeutic potential. The cell source differentiated from hiPSCs requires xeno‐free and robust methods for lineage‐specific differentiation. Here, a system is described for differentiating hiPSCs on new generation laminin fragments (NGLFs), a recombinant form of a laminin E8 fragment conjugated to the heparan sulfate chains (HS) attachment domain of perlecan. Using NGLFs, hiPSCs are highly promoted to direct differentiation into a paraxial mesoderm state with high‐efficiency muscle lineage generation. HS conjugation to the C‐terminus of Laminin E8 fragments brings fibroblast growth factors (FGFs) bound to the HS close to the cell surface of hiPSCs, thereby facilitating stronger FGF signaling pathways stimulation and initiating HOX gene expression, which triggers the paraxial mesoderm differentiation of hiPSCs. This highly efficient differentiation system can provide a roadmap for paraxial mesoderm development and an infinite source of myocytes and muscle stem cells for disease modeling and regenerative medicine.

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